The goal of this research is to define the mechanism(s) by which progesterone (P) increases which progesterone (P) increases prolactin secretion in estrogen (E)-primed nonhuman primates. Lactotropes do not contain progestin receptors (PR) and hence the action of P on prolactin is probably mediated by the CNS. In the monkey hypothalamus, E induces progestin receptors (PR), and PR is maintained with supplemental P treatment. This pattern differs from other reproductive tissues and may be due to a tissue specific expression of the A and B isoforms of PR. Dopamine neurons in the arcuate nucleus, which tonically inhibit prolactin, do not contain PR in monkeys, but do show a decrease in mRNA for tyrosine hydroxylase with E+P treatment. Likewise, oxytocin neurons which may stimulate prolactin, do not contain PR, but show an increase in oxhytocin content with ovarian steroids. Thus, the action of P on prlactin regulatory neurons is transduced by afferent neurons. Serotonin (5HT) beta-endorphin (BE) and GABAergic neurons exhibit an induction of PR with E treatment and maintain expression of PR upon addition ofP to the E regimen, but only 5HT increases with E+P treatment in guinea pigs. We hypothesize that 5HT stimulates BE and GABA neurons which in turn, inhibit the arcuate dopamine neurons. Work in progress will determine whether E+P increases the expression of the mRNAs fro trypotphan hydroxylase and tthe serotonin reuptake transporter. IN addition, we are characterizing the ratio of the isoforms of PR in brain, pituitary and reproductive tract of steroid-treated monkeys using Western blotting. Future studies will determine whether BE aand GABA neurons express mRNA for the stimulatory 5HT2A or 2C receptors and whether the dopamine neurons express mRNA for the inhibitory 5HT1A or 1Db receptors.